Motivators and barriers towards clinical research participation: A population-based survey from an Arab MENA country

Jordan was the first Arab country to enact clinical research regulations. The country has a well-flourished pharmaceutical industry that leans heavily on clinical research (CR) for drug development and post-marketing surveillance. In this cross-sectional study, we sought to assess the public’s awareness and attitude towards CR as well as their perceived motivators and barriers to CR participation. A population-based, self-administered questionnaire was distributed to the general public in Jordan. Among the 1061 participants in this survey, 74% reported being aware of CR. The majority (70%) agreed to the role of CR in health promotion. Online information and healthcare staff were the two main sources of CR information for the participants. About 25% of the participants received prior invitations to participate in CR with 21% agreeing to participate. However, most participants of the current study (63%) were willing to participate in future CR. Contributing to science, benefiting others, and promoting one’s own health were the top motivating factors for participating in CR; while time constraints, fear of research procedure, and lack of interest were the most cited reasons for rejecting participation. Filling out questionnaire surveys, donating blood samples, and participating in physical examinations were the main CR contributions of the participants. Nearly 31% of the participants believed that CR is conducted in a responsible and ethical manner, while 57% did not have an opinion regarding the same matter. In addition, 49% and 44% were neutral with regards to the degree of harm and confidentiality posed by CR. While only 27% disagreed that CR exposes participants to some form of harm, 48% either strongly agreed (15%) or agreed (33%) that it maintains high level of confidentiality for participants. The current study provides insight into the public’s perception of CR in Jordan as well as its motivating factors and perceived barriers towards participating in CR. We envisage to utilize this insight as an aid in the design of vigilant future awareness campaigns and recruitment strategies.

Introduction engagement in research. Contributing to science and altruism were the most cited facilitators to research participation while time commitments, worries regarding the research process, and lack of interest were the main perceived barriers to participation. In addition, the study revealed a great lack of opinion when it comes to CR ethical conduct, confidentiality, and harm which seems to originate from lack of prior CR participation experience. More importantly, prior participation in CR was associated with positive attitudes towards CR and future participation, which suggests public engagement in clinical studies is an effective tool to promote positive attitudes to CR. These findings, along with the recommended recruitment interventions discussed here, considering the identified participation motivators and barriers, will greatly assist in the implementation of effective and informed recruitment strategies which we envisage to override current CR recruitment challenges in the country.

Study design
The paper-based questionnaire was carefully constructed by reviewing similar surveys from the region [20,21,30,32,33]. The survey utilized diverse question formats including multiple choice, "Yes" or "No", multiple checkboxes, and Likert scale questions. The questionnaire consisted of four sections. The first section collected socio-demographic characteristics of participants including gender, age, nationality, marital status, education level, employment status, health insurance status, and chronic medical condition status. The second section assessed participants' awareness of "clinical research". The third section assessed participants' motivators as well as their perceived barriers towards participating in CR. The last section assessed participants' attitudes towards CR. Since Arabic is the native language of the country, the survey was translated from English to Arabic before deploying it to the public. Convenient sampling approach was used when sampling in the current study. Convenient sampling is the most commonly used non-probability sampling method that is based on approaching respondents who are "convenient" to the researcher, for instance by being located in reachable and accessible locations [34][35][36]. The study and questionnaire, both the Arabic and English versions, were approved by Jordan University of Science and Technology (JUST) Institutional Review Board (IRB) committee (Ref# 38/117/2018) with no consent form requirement.

Study participants
The paper-based questionnaire survey was deployed to potential participants who met the selection criteria, which include an age of more than 18 years old, competency, and the ability to read and understand the Arabic language. Potentially eligible participants were conveniently approached, by trained research assistants and qualified graduate students, in public areas (markets, parks, universities, restaurants/cafeterias/coffee bars) and in different cities (Amman, Irbid, Zarqa, Mafraq, and Karak) to participate in this self-administered questionnaire. Informed verbal consent was obtained from participants after they were provided with a detailed description of the study as well as contact information should they decide to withdraw or have any concerns regarding the study. The participants were then provided a brief explanation of the meaning of clinical research and its scope. Responses were collected over a onemonth period (between February and March 2019).

Data analysis and figure preparation
Statistical Package for Social Science (SPSS1) V21 (SPSS Inc., Chicago, IL, USA) was used to analyze the data. Power analysis was carried out ensuring power is more than 80%. Descriptive statistics were utilized to summarize the data. All numerical information was reported as numbers and percentages out of the total responses with percentages approximated to zero decimal places in the main text. Chi-square test was used for cross-tabulation analysis of independent variables with the outcome variable of interest. A two-sided P-value of less than 0.05 was considered statistically significant. Figures were prepared using Microsoft Excel 13.

Participants' awareness of "clinical research"
The majority of participants reported being familiar with "Clinical Research" (74%, n = 785) as well as its role in improving general health (70%, n = 740). Most participants reported online websites and healthcare providers as the two main sources of CR information that they have previously consulted (45%, n = 473 and 24%, n = 252 respectively), or would like to consult (26%, n = 279 and 24%, n = 249 respectively) in the future. On the other hand, a relatively large proportion of the respondents (33%, n = 346) did not know which CR information source they should consult (Fig 1).

Participants' attitudes towards clinical research
Almost half of the respondents (57%, n = 604) had no opinion when it comes to whether CR is conducted in a responsible and ethical manner. Although 30% (n = 323) believed that CR is conducted responsibly and ethically, about 4% (n = 41) and 9% (n = 93) thought it is conducted in an unethical manner or by unqualified personnel, respectively. On the other hand, a  large percentage of participants were not sure if participating in CR maintains participants' confidentiality (44%, n = 470) or exposes them to any form of harm (49%, n = 518). However, many participants either strongly agreed (15%, n = 126) or agreed (33%, n = 348) that CR maintains a high level of confidentiality and disagreed (27%, n = 283) that it imposes any form of harm to the participant. There was a statistically significant difference in responding to attitude questions between those who previously participated in clinical studies and those who did not (Table 2).

Discussion
The increased prevalence and complexity of acute and chronic conditions and comorbidities, all have made it a difficult task to diagnose and treat illnesses and to provide optimal healthcare services in Jordan. For this reason, CR has become critically important in dealing with these challenges through informing clinical practice and improving healthcare services delivery. Because participants' recruitment is an important step towards performing CR [3,37], we therefore aimed in this population-based survey to investigate the public's awareness of CR as well as their motivating factors and perceived barriers towards CR participation, and to discuss our findings in light of others from the region. A nearly equal number of males and females participated in the current survey. The majority were young to middle aged, well educated, unmarried, unemployed, medically insured Jordanians with no chronic clinical conditions. The study took place in Jordan, which is a country with a young population and has the highest  , and free of chronic diseases, it is unsurprising that these were the main sociodemographic characteristics of the participants. Participating in CR implies being familiar with the concept of "clinical research" and its value in advancing science and promoting health [46][47][48]. Most participants (74%) reported being aware of "clinical research". This awareness level is more than that reported by Lebanese participants in another study, where 45% were aware of this term [32]. About 70% of the current participants agreed that CR can promote general health. This percentage is relatively lower than a qualitative pilot study from Egypt where all participants believed that CR could improve their health condition [49], yet higher than a study from Saudi Arabia where only 51% of participants thought it can improve their general well-being [21]. In terms of using CR

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information for addressing health-related concerns, about 53% of our participants have sought CR information before. Online websites were the main source of CR information for those participants, followed by healthcare staff. In fact, these two were also the main sources for those who were willing to search for CR information. These findings are not surprising as there are multiple trustworthy online information sources that are readily accessible in Jordan. Indeed, in the last decade, the internet has become an important medium for shopping, socializing, and obtaining reliable information. Additionally, due to its low cost, comprehensibility, reliability, and ease of accessibility, it has become, for many, the preferred source of information. Notably, our assessment of participants' awareness towards CR revealed that about 26% did not understand the term "clinical research", 21% did not have an opinion regarding CR benefits on health, and nearly 33% did not know which source they should use to search for information. We identify those participants as potential targets for future campaigns that aim to raise awareness towards CR key elements and its trusted sources of information.
In terms of CR participation, only a small number of participants (25%) have received prior invitations to participate in CR, of which 21% and 4% accepted and rejected participation, respectively, resulting in a calculated rejection rate of 16%. This suggests that the relatively high awareness of CR reported in this study by participants is not solely as a result of prior participation, but rather associated with other factors such as the high literacy rate (Pvalue < 0.0001), although those who previously participated were relatively more aware of CR than those who did not (P-value < 0.0001). This may also suggest that most recruitments in the country take place in clinical settings, leaving the general public out of the recruitment equation most of the time. Therefore, modifications to the local recruitment strategies to outreach this potentially eligible population is highly recommended to more accurately reflect the research findings [50]. In addition, the fact that a large percentage (63%) of the participants showed willingness to participate in future CR further supports this recommendation. Similar findings were observed in Qatar and Saudi Arabia, where 63% and 74% of participants showed positive attitudes towards participation [20,21]. On the other hand, around 16% of our participants rejected future participation in CR, which is a similar rejection rate reported by subjects who were previously invited to participate. Nonetheless, those who previously participated in CR were more willing to participate in the future compared to those who did not (P < 0.0001). In fact, the influence of previous participation in promoting positive attitude towards future participation has also been reported by Al-Tannir et al. (2016) in Saudi Arabia [21]. In our study, those who did not know if they would accept or reject future participation (21%) would probably want to know more of the type of CR and the potential risks and benefits associated with it before they can decide on participation [21,51].
Assessing motivators for CR participation revealed that contributing to science and benefiting others were the two major motivating factors for both prior and future participations in CR. Even though Jordan is a developing country (https://datahelpdesk.worldbank.org/ knowledgebase/articles/906519-world-bank-country-and-lending-groups) with a high unemployment rate (https://www.worldbank.org/en/country/jordan/overview), financial incentive was not among the top four motivators and was the least cited barrier for CR participation. Although monetary compensation [52] and self-benefits [49] have been reported in the literature as major facilitators to CR participation, our findings are more in agreement with those from high-income countries in the region such as Saudi Arabia, UAE, and Qatar [20,21,24]. One may argue that this sense of altruism in the Jordanian population has its moral roots, theological origin, or both, and manifested in welcoming a large number of refugees from conflict areas and may provide a sense of usefulness and satisfaction to the participants [11,53].
On the other hand, time constraints, worries from the research procedure, and lack of interest were the main cited barriers to CR participation. Time constraint as a barrier was also reported from the non-national Qatari population [20]. It could be the case that in a developing country such as Jordan, most of the general public have to work long hours to make a living. This is in addition to the increased unemployment rate resulting from the recent population expansion; all of which make time a valuable asset to Jordanians [54]. Therefore, making the recruitment process as smooth and well organized as possible will most likely enhance public's participation. Additionally, fear regarding the research procedure reported in our study is not an uncommon hindrance to CR participation [4,55,56]. Such fear was reported to stem from perceived risks of interventions, their potential side effects, and/or confidentiality issues [57][58][59]. In this regard, improvements to the ethics and regulatory review procedures, improvements to the informed consent process, as well as efficient researcher-participant communication all have been reported to greatly enhance the recruitment procedure [54,[60][61][62][63]. The researcher can assure participants that the study was carefully designed to not cause harm to the participants and was approved by a research ethics committee which ensures that the study is conducted in compliance with ethical standards, and that their participation in the study will not be disclosed or impact their care or career [51]. The third most cited barrier to participation was lack of interest. Lack of interest in CR participation has been attributed to several reasons such as lack of health literacy and numeracy [64], lack of self-benefits [65], social/cultural constraints [66], unpleasant/unsatisfactory experience with prior participation [67], and/or lack of feedback from the researcher at the end of the study [68]. Most of these issues contributing to lack of interest in participation can be overcome through effective researcher-participant communication prior to, during, and after recruitment has taken place and will most likely enhance the recruitment process and participants retention [69,70].
Filling questionnaires, donating blood samples, and physical exam participation were the most highlighted previous contributions as well as the contributions participants were most interested-in in the future. Similar findings were observed in Qatar [20]. These results suggest that CR in Jordan that recruits a sample from the general population mostly demands these types of contributions. On the other hand, clinical trials, donating saliva samples, and donating tissue samples were the least cited prior contributions and the ones that participants were least interested in. Notably, prior participation in CR did not affect contribution interests as there was not a statistically significant difference in contribution interests between those who previously participated and those who did not. This suggests that future contribution interests may not be directly related to participants' prior experience with these CR contributions but rather the perceived degree of convenience and safety associated with them. Indeed, participants tend to be reluctant to participate in procedures that are largely invasive or that they perceive to involve a high degree of inconvenience [21,71].
Assessing participants' attitudes revealed that many participants did not have a clear opinion towards the ethical conduct (57%), confidentiality (44%), and harm (49%) associated with CR. The lack of opinion to these topics is not mainly arising from low education level or awareness as most participants were well-educated and aware of CR, but rather stems from a lack of prior experience in CR participation as the majority (80%) have not participated in a CR before. In support of this, cross-tabulation of prior participation with attitudes towards CR ethical conduct, confidentiality, and harm revealed a statistically significant difference (P values < 0.0001, <0.0001, and < 0.0109, respectively) [ Table 2]. We also envisage this lack of opinion to explain, at least in part, why 21% of participants were not sure if they would accept or decline future CR participation invites. More importantly, these findings suggest CR participation as an effective strategy to promote positive attitudes towards CR. In addition, although not assessed in the current study, several studies from Jordan highlighted ethical challenges in CR which include the IRB review process, the informed consent process, and lack of ethical training for researchers [72][73][74][75][76][77]. As a result, implementing research ethics guidelines as well as training in the responsible conduct of research would seem imperative to overcome those challenges [77,78].

Limitations
The current study comes with some limitations that can be mitigated through future research. First, the study did not assess participants' knowledge of key elements of CR, what it entails, or their misconceptions, rather, it assessed their awareness of and familiarity with the "clinical research" terminology. Although, the definition of CR and its scope were briefly explained to study participants, it is still a possibility that some study participants did not distinguish between certain closely related types of research such as CR versus public health research. Moreover, several other facilitators and barriers that can affect CR participation were not covered in the current study. For that matter, we only addressed the top cited motivators and barriers reported from previous studies in the region. Additionally, although the health care system in Jordan was greatly affected by the inflex of refugees from neighboring countries of conflict, this study did not assess the refugees' attitudes towards CR participation. Future studies that address refugees' knowledge of and attitudes towards CR will be of great value.
Moreover, although our study recruited participants from different areas of different cities, our sampling method, by definition, remains convenience sampling, and the ability to generalize from convenience sampling remains limited compared to random sampling. As a potential consequence of convenient sampling, the current study mostly recruited young participants, mainly excluding those aged 40 or above (Table 1). It could be argued that CR conducted in Jordan often recruits from populations with particular diseases, who in turn tend to be older in age. Therefore, this could be another explanation for the previously low CR participation rate of the respondents. Additionally, although Current results indicate that about 16% of the participants were non-Jordanian. The questionnaire used in the current study, however, did not inquire about the nationality of this group.

Conclusion
Clinical research participation of the public in Jordan needs improvement. The previously low CR participation rate of our sample reported in the current study originates from a lack of outreach to the public rather than a lack in their willingness to participate. Most of the Jordanian population are aware of CR and its role in promoting health. This awareness was associated with the high literacy rate of Jordanians and may reflect a research culture in the country. However, many participants lack or have negative attitudes when it comes to some aspects of CR such as ethical conduct, confidentiality, and potential harm. This comes largely because of lack of prior experience in CR participation. Therefore, modifying recruitment strategies to include more of the public in clinical studies in light of participation facilitators and barriers identified in this study is highly recommended in the early planning of CR to first reflect and generalize the findings of these studies to the general population and second to promote positive attitudes to CR.